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PubMed1999

Evaluation of trimethoprim and sulphamethoxazole as monotherapy or in combination in the management of toxoplasmosis in murine models.

The combination of trimethoprim (TMP) and sulphamethoxazole (SMX) is commonly used for the prevention of cerebral toxoplasmosis although there is no firm experimental basis to support this regimen. We used strain RH tachyzoites for challenge in the acute murine model of toxoplasmosis and found that TMP administered as a single agent, failed to eradicate toxoplasma even at the highest dose (70 mg/kg per day). SMX alone at 600 mg/kg per day, protected ten out of ten mice, although inoculation of brain from surviving animals to naive mice resulted in the development of an encephalitis. When combined, TMP (60 mg/kg per day) and SMX (300 mg/kg per day) protected ten out of ten mice and gave a 'cure' in four out of four mice. In the chronic cystogenic murine models, the combination TMP plus SMX administered from day 5 for 15 days or from day 28 for 288 days, gave protection and even apparent toxoplasmal eradication ('cure') at the highest dosing (60/300 mg/kg per day). However, microscopic severe encephalitis was found in mice classified as 'cured' after reinoculation. This result makes the interpretation of 'cure' very difficult. In conclusion TMP and SMX act synergistically, SMX being the more active arm of the combination. The combination was efficient in preventing the lethal development of chronic toxoplasma encephalitis, but did not guarantee complete recovery.

Animals↗

PubMed2003

Development of a vaccine for toxoplasmosis: current status.

The need for a vaccine for human toxoplasmosis is briefly discussed. Recent progress in knowledge of the protective immune response generated by Toxoplasma gondii and the current status of development of a vaccine for toxoplasmosis are highlighted.

Animals↗

PubMed2000

Evaluation of serodiagnosis of toxoplasmosis by using the recombinant nucleoside triphosphate hydrolase isoforms expressed in Escherichia coli.

The nucleoside triphosphate hydrolase (NTPase) isoforms termed, NTPase-I and NTPase-II of Toxoplasma gondii, were expressed in Escherichia coli as inclusion bodies and purified under denaturing condition. Furthermore, NTPase-I was refolded as an active form and purified under non-denaturing condition. The purified NTPase isoforms, both denatured and refolded, were tested for their usefulness as antigens for the serodiagnosis of acute toxoplasmosis in immunocompetent humans. The test was conducted by using the recombinant NTPase isoforms and comparing the enzyme linked immunosorbent assay (ELISA) absorbances with the Sabin-Feldman dye test titer. Seventy-three sera from dye test-positive patients, and 30 sera from subjects with no T. gondii infection were examined. The total positive rates in dye test positive sera were: 82% (60/73) for denatured NTPase-I; 78% (57/73) for denatured NTPase-II; and 63% (46/73) for refolded NTPase-I. For all three antigen types of recombinant NTPase, the positive rates of sera of acute toxoplasmosis suspected patients were 93% (13/14). A moderate correlation between the ELISA absorbance using these antigens and the dye test titer was observed with the correlation coefficients, 0.583 (r2) for denatured NTPase-I, 0.472 (r2) for denatured NTPase-II, and 0.604 (r2) for refolded NTPase-I in the linear regression analysis. There was no significant difference observed in the antigenicity between refolded and denatured NTPase-I, nor between the isoforms.

Acid Anhydride Hydrolases↗

PubMed1991

Intraglandular toxoplasmosis lymphadenitis of the parotid gland.

Toxoplasmosis is a protozoan infection manifested by systemic findings as well as generalized or localized lymphadenopathy. Although lympadenitis is the most common clinical form, involvement of the intraglandular nodes within the parotid gland found is a rare occurrence during the course of the disease. This unusual form may mimic a parotid mass, and can cause difficulties in differential diagnosis. In this article, a case of intraglandular parotid lymphadenitis which developed due to toxoplasmosis is presented, and the relevant literature is reviewed.

Adolescent↗

PubMed1982

Minocycline in the chemotherapy of murine toxoplasmosis.

The effects of minocycline alone or in combination with sulphadiazine were evaluated against acute murine toxoplasmosis and compared with the efficacy of pyrimethamine and sulphadiazine. The date presented show that mice could be protected from acute toxoplasmosis by minocycline, in spite of using a virulent strain of Toxoplasma gondii, a large inoculum, and a delay in the administration of the drug. Acute toxoplasmic infection in mice could be eradicated by aminocycline--sulphadiazine combination, which was found to be as effective as pyrimethamine--sulphadiazine combination therapy.

Animals↗

PubMed1989

Relationship between the production of interferon-alpha/beta and interferon-gamma during acute toxoplasmosis.

Acute toxoplasmosis was induced in mice, and interferon (IFN) production in serum and by spleen cells was evaluated during the infection period. Interferon was characterized by acid-treatment and anti-IFN-alpha/beta neutralization. In order to verify the correlation between the unusual aspects of the IFN production and the induction of immunosuppression, splenocyte mitogen responsiveness was investigated concomitantly to IFN synthesis. The activity of Toxoplasma-induced serum IFN-alpha/beta increased gradually throughout all post-infection days, but IFN-gamma was not detected in the systemic circulation at any time during the infection. It was also observed that IFN-alpha/beta production and the capacity to produce IFN-gamma by spleen cells were closely and inversely correlated. As the infection progressed, more IFN-alpha/beta was produced, and the ability of spleen cells to produce IFN-gamma decreased. The observation that Toxoplasma-infected mice were concomitantly immunosuppressed (as documented by mitogen unresponsiveness and defective IFN-gamma production) in direct correlation to IFN-alpha/beta production, suggests that such IFN-alpha/beta production is an important factor associated with acute toxoplasmosis-induced immunosuppression.

Acute Disease↗

PubMed2005

Ocular toxoplasmosis in mice: comparison of two routes of infection.

This paper aims to test the influence of route of infection (intravitreal and instillation) on the course of ocular toxoplasmosis in mice, using the Toxoplasma gondii Me-49 strain. All mice inoculated intravitreally or by instillation presented the same pattern of infection. Using either route, parasites were observed in the retinal vessel with the formation of a glial reaction in the inner plexiforme layer and discontinuity of the pigmented epithelium of the retina 7 days after infection. However, when the intravitreal route was used a more intense inflammatory infiltrate was observed in the retina. The results suggest that inoculation route remarkably influences the inflammatory pattern in ocular toxoplasmosis and that the instillation route should be preferentially used in experimental infections in the murine ocular model of infection by T. gondii, specially with small animals where there is extensive needle damage, which is not observed in the instillation route.

Animals↗

PubMed1990

Serological study of the prevalence of toxoplasmosis in asymptomatic patients infected with human immunodeficiency virus.

Asymptomatic individuals seropositive for antibody to human immunodeficiency virus (HIV) were investigated for the presence of toxoplasma specific antibody. Serological examination was performed using multiple assays. Of 500 patients studied 133 had serological evidence of previous exposure to Toxoplasma gondii. Specific IgM was detected in 7 patients using ISAGA and 2 patients by DS-ELISA. The immunoglobulin-G annual seroconversion rate was calculated to be 0.75%. The results of this study indicate 27% of HIV positive patients in the UK are at risk of developing life-threatening secondary reactivation of cerebral toxoplasmosis in association with AIDS. A further 0.5-1% per year may suffer primary toxoplasmosis.

Adolescent↗

PubMed2001

Disseminated toxoplasmosis after bone marrow transplantation: report of 9 cases.

Toxoplasma infection following bone marrow transplantation (BMT) is infrequently reported. We report 9 cases of disseminated Toxoplasma gondii infection in BMT recipients documented during an 11-year period at our institution. The incidence of T. gondii infection in our institution (1.14 per 100 allogeneic BMT) is higher than previously reported. The most frequently affected sites were the brain, lungs, and heart. Findings common to most patients who developed toxoplasmosis were positive pre-transplant serology, allogeneic transplant and graft-versus-host disease and its treatment, as well as BMT from matched unrelated donors. All 9 patients died and 8 were diagnosed only after autopsy. Heightened awareness of the occurrence of toxoplasmosis in marrow recipients, especially in highly endemic areas, and early diagnosis and therapy are needed for a better outcome.

Adolescent↗

PubMed1999

Successful treatment of cerebral toxoplasmosis in a marrow transplant recipient: contribution of a PCR test in diagnosis and early detection.

We report successful treatment of cerebral toxoplasmosis in an unrelated donor marrow transplant recipient. The clinical diagnosis was confirmed by polymerase chain reaction (PCR) amplification for T. gondii-DNA performed both on cerebrospinal fluid and blood leukocytes. Retrospective testing of stored blood samples demonstrated positive leukocyte PCR signal detected up to 52 days prior to onset of clinical symptoms. This case highlights the value of PCR in the diagnosis and early detection of cerebral toxoplasmosis.

Adult↗

PubMed2000

Diagnosis of toxoplasmosis in bone marrow transplant recipients: comparison of PCR-based results and immunohistochemistry.

Toxoplasmosis in bone marrow transplant recipients is a rare but serious complication and if untreated, almost uniformly fatal. The diagnosis, however, remains difficult. We therefore compared serial determination of antibody titers specific for T. gondii before and after transplantation, serial PCR for T. gondii DNA in serum, PCR and nested PCR for T. gondii DNA in various tissues, conventional histology and immunohistochemistry for detection of parasites in three patients with autopsy-confirmed toxoplasmosis after bone marrow transplantation. Immunohistochemistry demonstrated the presence of parasites in 13 out of 20 organs investigated (65%), whereas PCR detected T. gondii-specific DNA in 15 out of 20 organs (75%). Immunohistochemistry revealed concordant results to PCR data in 60% of the specimens. With the use of a nested PCR protocol, eight out of nine samples (89%) were positive for T. gondii-specific DNA. The combination of both methods detected the presence of parasites in 90% of the specimens. Serial PCR in serum did not yield positive results. Neither PCR nor immunohistochemistry was able to detect parasites in all organs investigated, but both methods together improved sensitivity to 90% and consequently, should be used jointly to maximize diagnostic precision. Bone Marrow Transplantation (2000) 25, 1257-1262.

Adult↗

PubMed1998

Cutaneous and gastrointestinal mastocytosis associated with cerebral toxoplasmosis.

A patient with systemic cutaneous and gastrointestinal mastocytosis and associated meningoencephalitic toxoplasmosis is reported. The simultaneous occurrence of the two conditions and their regression after treatment of the toxoplasmosis suggest a possible relationship between the mast cell proliferation and the parasitic infection. Mast cell activation and stimulation may be transitory in response to a stimulus, causing reactional mastocytosis.

Adult↗

PubMed1998

Assessment of the activity of atovaquone-loaded nanocapsules in the treatment of acute and chronic murine toxoplasmosis.

The aim of this work was to develop a new pharmaceutical form of atovaquone and to study its activity against Toxoplasma gondii in vitro and in vivo. Nanocapsules were chosen as the oral dosage form of administration. An analytical method was developed to determine the drug content in nanocapsules. The stability of these nanocapsules were assessed by following drug content, size, pH and osmolarity for a period of six months. The in vitro activity of atovaquone-loaded nanocapsules against tachyzoites of T. gondii (RH stain) was comparable to its suspension form. In vivo studies were carried out in murine models of acute and chronic toxoplasmosis. Mice acutely infected with the virulent RH strain were orally treated with a dose regimen of 15 mg/kg/day for 10 days, starting from day 1 post-infection. 75% of the mice receiving atovaquone-loaded nanocapsules survived 30 days post-infection, compared to none of untreated controls and none of mice treated with the suspension with the same dose regimen. In mice chronically infected by the COUL or the ME49 strain (Type II strains), then treated for six weeks, treatment with atovaquone (15 mg/kg/d, nanoparticles or suspension) resulted in a decrease of brain parasitic burden, which was significantly more pronounced in ME49-infected mice and in those treated with drug-loaded nanocapsules. These results show that the sensibility of T. gondii to atovaquone is different according to the strains and that the activity of atovaquone in the treatment of toxoplasmosis is enhanced when administered in nanoparticular form.

Acute Disease↗

PubMed1999

Experimental congenital toxoplasmosis in Wistar and Holtzman rats.

Congenital toxoplasmosis was evaluated in Wistar and Holtzman rats using two strains of Toxoplasma gondii isolated in Brazil. Pregnant rats were inoculated by subcutaneous or intraperitoneal routes with 10(6) or 8 x 10(6) tachyzoites of N strain (virulent for mice) and by subcutaneous or oral routes with 10(2) or 1.2 x 10(3) cysts of P strain (avirulent for mice). The tissues of rat pups born from these rats were bioassayed for T. gondii infection. T. gondii was not observed in the pups born from rats inoculated with N strain. In the animals inoculated with P strain, congenital toxoplasmosis occurred in 22.8% (Wistar rats inoculated with 10(2) cysts by the subcutaneous route), 11.4% (Wistar rats inoculated with 10(2) cysts by the oral route), 21.2% (Wistar rats inoculated with 1.2 x 10(3) cysts by the oral route) and 2.9% of fetal infection (Holtzman rats inoculated with 10(2) cysts by the oral route). None of the pups born from chronically infected mother were infected with T. gondii.

Administration, Oral↗

PubMed2000

Toxoplasmosis in beluga whales (Delphinapterus leucas) from the St Lawrence estuary: two case reports and a serological survey.

Toxoplasmosis was diagnosed in two free-ranging beluga whales from the St Lawrence estuary, Quebec, Canada, in 1988 and 1998. Histologically, tachyzoites and bradyzoites were present in the brain, spleen, lymph nodes, adrenals and lungs of both animals, and in the thymus of one. These organisms were readily labelled by an indirect immunohistochemical method for Toxoplasma gondii antigens. In the lymph nodes, spleen and lungs the organisms were associated with histiocytic infiltration. In the brain of one animal they were associated with mild multifocal gliosis and haemorrhages. There was no evidence of concomitant morbillivirus infection. Serum samples were collected from 22 beluga whales stranded between 1995 and 1998 on the shores of the St Lawrence Estuary and examined for antibodies to T. gondii by the modified agglutination test. Antibody titres of s25 were found in six (27%) of the animals. This is the first confirmed report of toxoplasmosis in beluga whales.

Animals↗

PubMed1996

[Treatment of toxoplasmosis retinochoroiditis with atovaquone in an immunocompetent patient].

BACKGROUND: In Central Europe ocular toxoplasmosis is the leading cause of posterior uveitis. It is a major cause of severe visual loss and blindness in young people. Drugs for treatment of active lesions (tachyzoites) have been available for decades but are seen controversial especially because of sometimes serious side effects. These drugs don't seem to shorten the active inflammation nor the recurrence rate, in particular because of the poor effect on the cystic form (bradyzoites). Atovaquone (hydroxynaphthoquinone) is well tolerated systemically and is effective against tachyzoites and bradyzoites of Toxoplasma gondii so that we hope to reduce the recurrence rate. PATIENT HISTORY AND CLINICAL FINDINGS: Two immunocompetent patients with the first and respective second symptomatic recurrence of unilateral active toxoplasmic retinochorioiditis located within the major temporal vascular arcades were treated with Atovaquone and Fluorocortolone because of an impending loss of central visual function. THERAPY AND CLINICAL COURSE: Under the treatment with Atovaquone (3 x 750 mg/day) for three weeks and tapering of the Fluorocortolone the active lesions healed quickly. After a few weeks, atrophic and remarkably little pigmented scars remained. No side effects were observed. After a period of 7 and respective 11 months no recurrence occurred. CONCLUSIONS: Atovaquone is an effective and well tolerated drug for the treatment of active ocular toxoplasmosis in immunocompetent patients. Its efficacy against tachyzoites and cysts of Toxoplasma gondii relative to other drugs remains to be determined by further clinical trials.

Adult↗

PubMed1999

Neurologic manifestations of toxoplasmosis in AIDS.

Central nervous system (CNS) toxoplasmosis is the most common cause of cerebral mass lesions in AIDS patients. Toxoplasma gondii is commonly acquired through ingestion of contaminated meats resulting in latent infection. With the onset of immunosuppression, it may preferentially infect the CNS, resulting in a wide range of clinical presentations. Effective antibiotic therapy is available and capable of producing rapid remission of active infection but must be continued throughout life to prevent recurrence. Characteristic presentations and rapid therapeutic response permit presumptive diagnosis and initiation of specific antibiotics in many cases; however, appropriate clinical and radiographic monitoring to detect alternative or mixed pathologies is necessary. Unusual presentations may hinder rapid diagnosis and should be considered in AIDS patients with cryptic CNS symptoms. Despite increasing attention to primary prophylaxis, the worldwide distribution of this parasite, its potential to be the presenting illness in previously unidentified human immunodeficiency virus-infected individuals, and failures of prophylaxis are likely to make toxoplasmosis an important continuing source of neurologic morbidity in AIDS.

Animals↗

PubMedDate not supplied

[Acquired toxoplasmosis with cerebral involvement and subsequent hearing loss].

In immunocompetent patients the postnatally acquired toxoplasmosis is usually a mild or asymptomatic disease. CNS manifestations are rare, e.g. in patients with HIV infection or in patients with other types of immunosuppression. We report on a 9-year old healthy boy, who was hospitalized after one week with subfebrile temperatures and headache with clinical signs of encephalitis and unilateral deafness. We diagnosed a toxoplasmosis and treated the patient with pyrimethamine and sulfadiazine. While most of the signs and symptoms disappeared rapidly the deafness persisted.

Anti-Infective Agents↗